The reliable monitoring of the depth of anesthesia has remained as one of the main challenges during the past ten years or so while measurement of most of the other key physiological parameters for comprehensive patient monitoring has practically reached a level of maturity. One of the reasons is that the concept of depth of anesthesia, when applying the modern concept of balanced anesthesia, is not a one-dimensional parameter, but has no less than five components. A balanced high quality anesthesia consists of adequate hypnosis, analgesia, muscle relaxation, suppression of the autonomous nervous system and blockade of the neuromuscular junction. Hypnosis means loss of consciousness down to a level able to guarantee amnesia, i.e. that no memories about the operation appear afterwards. Analgesia means that no pain is felt during the surgery. Sufficient muscle relaxation is required to ensure optimal operating conditions for the surgeon manipulating the tissue. The autonomous nervous system, if not suppressed, causes the patient to respond to surgical activity by shock reaction which affects heavily on the hemodynamics and endocrine system. To keep the patient completely motionless, the neuromuscular junction transmitting the orders from the brain to the muscles needs to be blocked, which means complete paralysis of the body. One practical consequence of the paralysis is that the patient also needs to be connected to a mechanical ventilator because the breathing muscles also become inoperative.
To achieve the state of balanced and adequate anesthesia, several different types of drugs are needed. For hypnosis one needs a drug affecting directly on the brain. Such a drug can be either inhalational anesthetics administered as a vapor into the lungs or intravenous agents infused into the blood circulation. Many of the hypnotically acting drugs also have an useful effect on pain, autonomous nervous system response, and muscle relaxation. However, special, dedicated drugs affect best on pain and neuromuscular blockade. What makes this complex picture even more difficult is that the practices of anesthesia vary from country to country and also among individual anesthesiologists. There are also schools of scientists that emphasize the weight of the components of the anesthesia in differing ways.
The importance of reliable monitoring of the depth of anesthesia has both safety and economy related aspects which are partly coupled one to another. Too light anesthesia and especially waking up in the middle of an operation may become an extremely traumatic experience both for the patient and the anesthesiologist. Unnecessarily deep anesthesia means increased costs in use of drugs most of which are rather expensive. Too deep anesthesia usually also affects the quality of the postoperative period and may increase time required for active recovery care.
Even though the importance of taking care and need to monitor all five components of the anesthesia is widely acknowledged, hypnosis has remained as the most difficult task because it is related to the challenging measurement of the level of consciousness which on a wider context also is a philosophical problem. Technically speaking, however, a solution able to quantify the brain activity on a consistent continuous scale extending from full alertness to maximally deep, but reversible, sleep can be considered adequate for the anesthesia purpose, if it is robust enough for the use of different drug cocktails in different individuals. Traditionally the attempts to develop methods and measurements for this purpose have been based on monitoring the electrical activity of the brain based on the weak biosignals picked up with electrodes on the skull surface. This method is called electroencephalography (EEG).
The complex EEG signal having close to random nature at first sight can be analyzed by many signal processing approaches which have developed to high level sophistication since the early days when the first findings about the change of spectral contents of the EEG signal as related to depth of consciousness were published. Generally speaking the EEG signal moves to lower frequencies when the sleep gets deeper and finally reaches a state called xe2x80x9cburst suppressionxe2x80x9d when the signal is silent most of time with short intermediate bursts of electrical activity. The latest achievement in the EEG processing is the xe2x80x9cbispectral indexxe2x80x9d, the BIS by Aspect Medical, which in addition to some conventional spectral analysis methods pays attention to the phase coupling between various EEG frequency pairs produced by nonlinear interaction in the electrical activity. What the actual connection of this component, which might reflect the number of independent xe2x80x9coscillatorsxe2x80x9d in the brain, is to the level of consciousness is not well understood. Therefore, the BIS number on a scale from 100 down to zero when moving from alertness to deepest possible sleep, is a semi-empirical combination of various EEG features based on profound statistical analysis of a wide data base collected during thousands of anesthesias. The BIS is based on the processing of not only the spontaneous EEG activity, but also on evoked potentials, the response of the brain to external stimuli, which have been proposed to be used to monitor the level of consciousness. These may be, for example, audible clicks to the ear, or light electrical impulses to the nerves. The former are called acoustic evoked potentials (AEP) and the latter somatosensory evoked potentials (SSEP).
The generic problem of the EEG and evoked potentials in anesthesia application is the artifacts caused by external electrical interference from the other devices, especially the electrocautery machine, which is known as the electrical knife. Additionally the attachment procedure of the EEG electrodes is often considered as consuming too much time in the streamlined fast modern anesthesia process. An additional drawback related both to raw EEG and evoked potentials is the limited speed of response, because both methods require collection of data for a certain period of time, typically at least 5 seconds, and on the top of that some additional time for computing. This can become a problem especially when trying to detect if the patient is waking up from too light an anesthesia which happens very fast because of the physiological cascade mechanisms involving positive feedback loops.
The purpose of this invention is to present a new approach to quantify the relevant brain activity status and its connection to the level of consciousness especially related to the adequacy of the hypnotic component of the depth of anesthesia. It is based the results of many recent findings of basic brain research which has been able to confirm the close physiological links between the electrical activity of the brain and the functional control of the blood and oxygen delivery to the neurally activated part of the brain. This is also coupled with the local metabolic activity reflected as increased glucose metabolic rate. See articles 1, 2 in the list of references. The methods which have illuminated this field the most include positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and near infrared spectroscopy (NIRS).
Technically the NIRS method differs from the two others mentioned above as being much more simple and less expensive. Human tissue including the brain cortex is transparent for near-infrared (NIR) light into depth of several centimeters. The optical wavelengths suitable for this purpose are typically between 700 and 900 nanometers. The NIR spectroscopy has been employed in commercial devices like the Somanetics Invos 300 and Hamamatsu NIRO 500 with a purpose to monitor oxygenation of the cerebral blood. These devices have been designed primarily to be used during carotic artery surgical procedures to give a warning of development of ischemia on the brain tissue. Recent studies (3,4) have indicated that these two devices seem not to measure the same parameter and either of them may not be fully specific and reliable in measuring the brain tissue oxygenation.
On the other hand, the prior art includes pulse oximeters which have developed to a well established technology, being able to measure non-invasively the oxygen saturation of the hemoglobin in the arterial blood with an accuracy comparable to laboratory blood gas analysis. The idea of the pulse oximeter is to use the pulsation of the arterial blood volume, typically at the finger tip, to extract the information from the arterial blood only, and excluding the venous blood and the tissue effects. Thus it is essentially only the AC-component of the optical signal which is utilized. The pulse oximeter also uses two wavelengths chosen to differentiate maximally between the absorption of the light by oxygenated and non-oxygenated hemoglobin. All the additional information included in the DC component of the optical signal and related to the absorption and scattering by the venous blood and tissue is discarded.
However, the brain tissue structure represents a major challenge for pulse oximetry, since the pulsation of the blood in the high density network of intertwined blood capillaries and neuron branches (axons and dentrites) is highly attenuated. It then becomes very difficult to differentiate between oxygenation of arterial and venous blood and the signal is more like a weighted average of both values. In these conditions one can hypothesize that, regarding the received optical signal, the scattering properties of the tissue become more important than the absorption properties.
The scattering of the light from a medium depends on the density and characteristic dimensions of the microscopically tiny structures or particles, xe2x80x9cthe scatterers.xe2x80x9d In the brain these consist of the circulating blood cells, the micro-capillaries of the cerebral circulation and the neural cells or the neurons. It has been proven (5) that the regulation of the blood flow in the microvascular bed is coupled with the tissue metabolic demands, which varies with the functional activity. It has also been shown that gaseous nitric oxide, a well known vasodilator, acts as a mediator in this process. When a neuron is activated to perform a task some energy is required for the related electrochemical reaction. This is taken from the blood stream, typically as glucose, and some oxygen is needed for the process to convert the glucose to energy. The ingenious control mechanism of the brain to supply enough oxygen to the activated areas works, in a simplified view, so that the microvessel servicing each neuron is dilated to direct more flow to the cell when NO is released at the moment of activation. The neurons themselves have also been shown to change their physical dimensions by swelling during the activation. The dilation of the vessels also means increased blood volume locally. More blood contains more hemoglobin in the space of interest which also affects on the overall scattering and absorption and the output signal.
These couplings related to the brain activation during anesthesia have been studied recently by the PET method and the images reveal that the rate of glucose metabolism during inhalation anesthesia decreases in a consistent manner both during inhalational and propofol anesthesia (1,2). Additionally, to prove the coupling between metabolic and electrical activity, it was shown that the whole-brain glucose metabolism is practically directly proportional to the EEG based bispectral index BIS and the local variations are small (2). Also a simple single channel (NIRO 500) local NIR oxygenation measurement on the forehead of a subject rapidly and consistently seems to react on the loss of consciousness during induction with some intravenous agents (6,7) even if the amplitude and direction of the response varied between the agents.
The present invention exploits the above mentioned documented findings supporting the existence of a direct coupling between the local brain activation level and the size (diameter) of both the blood microvessels and the neurons, as well as the increasing amount of blood in the measurement space. According to well known physical principles, the changes in the dimension and number of light scatterers of the medium change the optical path of photons from a light emitter to a light detector. This means that the output of the light detector in an arrangement where the light beam has interacted with the brain cortex tissue is proportional to the changes of the functional activation at the illuminated brain tissue site. The special application where this measurement would be of high practical value is the monitoring of the changes in the hypnotic component of the depth or adequacy of anesthesia. Also many critically ill patients in intensive care units require sedation and this method would also be useful in measuring changes in the level of sedation for titration of the sedative drugs.
The technical challenge is to tune the instrument to react primarily on the changes of the tissue scattering and not the oxygenation which is of secondary interest in this context. The molecular absorption coefficients, as a function of wavelength, differ considerable for oxyhemoglobin and reduced hemoglobin. This difference is exploited in pulse oximeters by using two wavelengths with great differences in the absorption. However, around 800 nm the absorption is equal for both and this is called xe2x80x9cthe isobestic point.xe2x80x9d This means that by using this wavelength the specificity to measure oxygen saturation is lost and the optical output is mainly dominated by changes in scattering and becomes sensitive for brain activation.
The practical measurement set-up would consist of one light detector and one or more transmitters or emitters. The transmitters can either be semiconductor LED""s or diode lasers which both are available for the wavelength around 800 nm, i.e. the isobestic point for hemoglobin. The brain tissue is a very strong scatterer and in addition the light has to transmit the skull bone twice so that the received light signal will be very weak. The photomultiplier tube is the most sensitive detector but state-of-the-art solid-state detectors, like special photodiodes, are also adequate for this purpose. The transmitter-detector set is attached preferably on the forehead of the subject to avoid problems caused by hair. The basic requirements for geometry are defined by the requirement that major part of the effective light path has to interact with the brain tissue and the direct path through the skin layer on the skull has to be minimized. A typical distance between transmitter and detector can be from 1 to 5 cm depending on whether direct backscattering or a longer banana shaped optical pathway is preferred.